TY - JOUR
T1 - Pembrolizumab in Combination With Erlotinib or Gefitinib as First-Line Therapy for Advanced NSCLC With Sensitizing EGFR Mutation
AU - Yang, James Chih Hsin
AU - Gadgeel, Shirish M.
AU - Sequist, Lecia Van Dam
AU - Wu, Chien Liang
AU - Papadimitrakopoulou, Vassiliki A.
AU - Su, Wu Chou
AU - Fiore, Joseph
AU - Saraf, Sanatan
AU - Raftopoulos, Harry
AU - Patnaik, Amita
N1 - Publisher Copyright:
© 2019 International Association for the Study of Lung Cancer
PY - 2019/3
Y1 - 2019/3
N2 - Introduction: Anti-EGFR agents are standard treatments for patients with EGFR-mutant advanced NSCLC. The feasibility of combining erlotinib or gefitinib with the anti–programmed death 1 immunotherapy pembrolizumab was evaluated in the phase 1/2 KEYNOTE-021 study (NCT02039674). Methods: Adults with previously untreated stage IIIB/IV EGFR-mutant NSCLC were treated with pembrolizumab 2 mg/kg intravenously every 3 weeks plus oral erlotinib 150 mg daily in cohort E or oral gefitinib 250 mg daily in cohort F, using a 3 + 3 design with cohort expansion. rTumor response was evaluated per Response Evaluation Criteria in Solid Tumors version 1.1 by blinded independent central review. The primary objective was determination of a recommended phase 2 dose. Results: Twelve patients enrolled to receive pembrolizumab plus erlotinib and seven to receive pembrolizumab plus gefitinib. No dose-limiting toxicities or grade 5 events occurred. Pembrolizumab plus erlotinib was feasible, with adverse events similar to those expected for monotherapy. However, pembrolizumab plus gefitinib was not feasible due to grade 3/4 liver toxicity in five of seven patients (71.4%), leading to permanent treatment discontinuation in four patients. The most frequently occurring treatment-related adverse events with pembrolizumab plus erlotinib were rash (50.0%), dermatitis acneiform, diarrhea, hypothyroidism, and pruritus (33.3% each). The objective response rate was 41.7%, including response in all four patients with programmed death ligand 1 expression 50% or greater. Conclusions: Although pembrolizumab plus gefitinib was not feasible, the toxicity profile observed with pembrolizumab plus erlotinib suggests combining immunotherapy with anti-EGFR therapy is feasible. Pembrolizumab plus erlotinib did not improve objective response rate compared with previous monotherapy studies; further evaluation would be necessary to evaluate potential effects on other efficacy outcomes.
AB - Introduction: Anti-EGFR agents are standard treatments for patients with EGFR-mutant advanced NSCLC. The feasibility of combining erlotinib or gefitinib with the anti–programmed death 1 immunotherapy pembrolizumab was evaluated in the phase 1/2 KEYNOTE-021 study (NCT02039674). Methods: Adults with previously untreated stage IIIB/IV EGFR-mutant NSCLC were treated with pembrolizumab 2 mg/kg intravenously every 3 weeks plus oral erlotinib 150 mg daily in cohort E or oral gefitinib 250 mg daily in cohort F, using a 3 + 3 design with cohort expansion. rTumor response was evaluated per Response Evaluation Criteria in Solid Tumors version 1.1 by blinded independent central review. The primary objective was determination of a recommended phase 2 dose. Results: Twelve patients enrolled to receive pembrolizumab plus erlotinib and seven to receive pembrolizumab plus gefitinib. No dose-limiting toxicities or grade 5 events occurred. Pembrolizumab plus erlotinib was feasible, with adverse events similar to those expected for monotherapy. However, pembrolizumab plus gefitinib was not feasible due to grade 3/4 liver toxicity in five of seven patients (71.4%), leading to permanent treatment discontinuation in four patients. The most frequently occurring treatment-related adverse events with pembrolizumab plus erlotinib were rash (50.0%), dermatitis acneiform, diarrhea, hypothyroidism, and pruritus (33.3% each). The objective response rate was 41.7%, including response in all four patients with programmed death ligand 1 expression 50% or greater. Conclusions: Although pembrolizumab plus gefitinib was not feasible, the toxicity profile observed with pembrolizumab plus erlotinib suggests combining immunotherapy with anti-EGFR therapy is feasible. Pembrolizumab plus erlotinib did not improve objective response rate compared with previous monotherapy studies; further evaluation would be necessary to evaluate potential effects on other efficacy outcomes.
KW - Combination therapy
KW - Erlotinib
KW - Gefitinib
KW - NSCLC
KW - Pembrolizumab
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U2 - 10.1016/j.jtho.2018.11.028
DO - 10.1016/j.jtho.2018.11.028
M3 - Article
C2 - 30529597
AN - SCOPUS:85061664921
SN - 1556-0864
VL - 14
SP - 553
EP - 559
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
IS - 3
ER -